基于网络药理学研究瓜蒌-薤白药对抗高脂血症作用机制

钟华; 仇静文; 吴鸿飞; 徐赫; 张鹏; 薛程姣; 贾鹏程

doi:10.13422/j.cnki.syfjx.20201603

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基于网络药理学研究瓜蒌-薤白药对抗高脂血症作用机制

数据挖掘 | 更新时间：2020-09-09

- 基于网络药理学研究瓜蒌-薤白药对抗高脂血症作用机制
- Mechanism of Action of Trichosanthis Fructus-Allii Macrostemonis Bulbus Herb Pairs Against Hyperlipidemia Based on Network Pharmacology
- 中国实验方剂学杂志 2020年26卷第18期页码：154-165
- 作者机构：
  
  安徽中医药大学药学院，合肥230000
- 作者简介：
  
  钟华，硕士，从事中药心血管药理学研究，E-mail：2773000234@qq.com
  吴鸿飞，博士，教授，从事中药心血管药理学研究，E-mail：wuhongfei2009@126.com
- 基金信息：
  
  国家自然科学基金项目(81873038);2018年大学生创新创业训练计划项目(2018173)
- DOI：10.13422/j.cnki.syfjx.20201603
  中图分类号： R2-0;R22;R285.5
- 收稿日期：2019-12-17，
  
  网络出版日期：2020-06-09，
  
  纸质出版日期：2020-09-20
- 稿件说明：
移动端阅览
钟华,仇静文,吴鸿飞等.基于网络药理学研究瓜蒌-薤白药对抗高脂血症作用机制[J].中国实验方剂学杂志,2020,26(18):154-165.

ZHONG Hua,QIU Jing-wen,WU Hong-fei,et al.Mechanism of Action of Trichosanthis Fructus-Allii Macrostemonis Bulbus Herb Pairs Against Hyperlipidemia Based on Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(18):154-165.
钟华,仇静文,吴鸿飞等.基于网络药理学研究瓜蒌-薤白药对抗高脂血症作用机制[J].中国实验方剂学杂志,2020,26(18):154-165. DOI： 10.13422/j.cnki.syfjx.20201603.

ZHONG Hua,QIU Jing-wen,WU Hong-fei,et al.Mechanism of Action of Trichosanthis Fructus-Allii Macrostemonis Bulbus Herb Pairs Against Hyperlipidemia Based on Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(18):154-165. DOI： 10.13422/j.cnki.syfjx.20201603.

摘要

目的

基于高脂血症大鼠模型和网络药理学技术分析瓜蒌-薤白药对抗高脂血症的作用机制。

方法

通过瓜蒌-薤白药对低、中、高剂量（1，2，4 g·kg

-1

·d

-1

）预防性给药高脂血症大鼠，检测血脂和炎症因子水平。采用中药系统药理学数据库和分析平台（TCMSP）和文本挖掘筛选瓜蒌-薤白药对活性成分，Swiss Target Prediction，Similarity ensemble approach（SEA），DrugBank数据库筛选与活性成分对应的作用靶点；通过Therapeutic Target Database（TTD），Online Mendelian Inheritance in Man（OMIM），DrugBank和DisGeNET数据库收集疾病靶点。整合交集活性成分的作用靶点和疾病靶点，并通过拓扑学参数筛选，获得瓜蒌-薤白药对抗高脂血症的主要候选靶点。通过ClueGO进行京都基因与基因组百科全书（KEGG）通路富集，the Database for Annotation，Visualization and Integrated Discovery（DAVID）数据库进行基因本体（GO）功能富集分析。通过Cytoscape构建中药-成分-靶点网络模型、靶点-通路网络模型，并分析其串扰靶点和信号通路。

结果

动物实验表明，瓜蒌-薤白药对预防性给药可明显降低高脂血症大鼠血清中总胆固醇（TC），甘油三酯（TG），低密度脂蛋白胆固醇（LDL-C）水平，升高高密度脂蛋白胆固醇（HDL-C）水平，抑制白细胞介素-6（IL-6），肿瘤坏死因子-

（TNF-

）表达（

0.05，

0.01）。亚油酸乙酯，香叶木素，

-菠菜甾醇等27个活性成分可能是“瓜蒌-薤白”药对主要药效成分，16个串扰靶点和10条信号通路可能是其主要药效靶点和通路；药对主要靶向载脂蛋白A1（APOA1），载脂蛋白A2（APOA2），载脂蛋白C3（APOC3），脂蛋白脂肪酶（LPL），低密度脂蛋白受体（LDLR）等串扰靶点影响胆固醇代谢、胆汁分泌、过氧化物酶体增殖物激活型受体（PPAR）信号通路调节脂质水平；靶向肿瘤坏死因子（TNF），IL-6，IL-1B，丝裂原活化蛋白激酶1（MAPK1），C-C基序趋化因子2（CCL2）等串扰靶点影响TNF信号通路，Toll样受体信号通路，白细胞介素-17（IL-17）信号通路，缺氧诱导因子（HIF）信号通路调节炎症因子水平。DAVID数据库进行GO富集分析，表明药对主要通过炎症反应、脂质定位、储存和脂质代谢等生物学过程治疗高脂血症。

结论

通过这些发现可预测瓜蒌-薤白药对干扰高脂血症的作用机制，为瓜蒌-薤白药对的物质基础和临床应用提供理论基础。

Abstract

Objective

Based on the hyperlipidemia rat model and network pharmacology technology

the mechanism of action of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs against hyperlipidemia was analyzed.

Method

The levels of blood lipids and inflammatory factors were measured through prophylactic administration of low

medium and high-dose Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs in hyperlipidemia rats. The active ingredients of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs were screened out through Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) and text mining. The targets of active ingredients screened through the Swiss Target Prediction

Similarity ensemble approach (SEA)

DrugBank database. The disease targets were collected through Therapeutic Target Database (TTD)

Online Mendelian Inheritance in Man (OMIM)

DrugBank

DisGeNET database. The targets of active ingredients and disease target were integrated

and screened through topological parameters to gain the main candidate targets of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs against hyperlipidemia. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and the gene ontology (GO) functional enrichment analysis were conducted through ClueGO and Database for Annotation

Visualization and Integrated Discovery (DAVID)

respectively. The traditional Chinese medicine-chemical ingredient-target network model

and the target-pathway network model were constructed through Cytoscape

and their crosstalk target and signal pathway were analyzed.

Result

Animal experiments showed that the prophylactic administration of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs significantly reduced the levels of total cholesterol (TC)

triglycerides (TG)

low-density lipoprotein cholesterol (LDL-C) in serum of rats with hyperlipidemia

increased high-density lipoprotein (HDL-C) levels

and inhibited the expressions of interleukin-6 (IL-6) and tumor necrosis factor-

(TNF-

). According to the findings

27 active ingredients

such as mandenol

diosmetin and

-spinasterol

might be the main active ingredients of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs

16 crosstalk targets and 10 signal pathways might be the main therapeutic targets and pathways

main targeting apolipoprotein A1 (APOA1)

apolipoprotein A2 (APOA2)

apolipoprotein C3 (APOC3)

lipoprotein lipase (LPL)

low-density lipoprotein receptor (LDLR) and other crosstalk targets affected cholesterol metabolism

bile secretion

peroxisome proliferator activated receptor (PPAR) signaling pathway in regulating the lipid level

targeting tumor necrosis factor (TNF)

IL-6

interleukin-1

(IL-1

)

mitogen-activated protein kinase 1 (MAPK1)

C-C motif chemokine 2 (CCL2) and other crosstalk targets affected tumor necrosis factor (TNF) signaling pathway

Toll-like receptor signaling pathway

interleukin-17 (IL-17) signaling pathway

and hypoxia inducible factor (HIF) signaling pathway in regulating the inflammatory factor level. The DAVID database for GO enrichment analysis showed that the hyperlipidemia was treated mainly through biological processes

such as inflammation

lipid localization

storage and lipid metabolism.

Conclusion

These findings can predict the mechanism of action of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs against hyperlipidemia

and provide a theoretical basis for the material basis and clinical application of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs.

关键词

Keywords

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